Dexketoprofen-vista

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXKETOPROFEN-VISTA (DEXKETOPROFEN-VISTA)

Composition:

Active ingredient: dexketoprofen;

One film-coated tablet contains 36.9 mg of dexketoprofen trometamol, equivalent to 25 mg of dexketoprofen;

Excipients: maize starch, microcrystalline cellulose, sodium starch glycolate (Type A), glyceryl distearate;

Film coating: tablet coating mixture Opadry Y-1-7000 [hypromellose (E 464), titanium dioxide (E 171), polyethylene glycol 400].

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, cylindrical, biconvex tablets with a score line and embossing "DT2" on one side.

Pharmacotherapeutic group. Anti-inflammatory and antirheumatic agents. Propionic acid derivatives. ATC code M01A E17.

Pharmacological properties.

Pharmacodynamics.

Dexketoprofen trometamol is a salt of propionic acid. It is an analgesic, anti-inflammatory and antipyretic medicinal product belonging to the class of non-steroidal anti-inflammatory drugs (NSAIDs).

The mechanism of action is based on reducing the synthesis of prostaglandins by inhibition of cyclooxygenase. Specifically, the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2 is inhibited, from which prostaglandins PGE1, PGE2, PGF2α, PGD2, as well as prostacyclin PGI2 and thromboxanes (TxA2 and TxB2) are formed. In addition, the inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of the medicinal product.

Pharmacodynamic action.

The inhibitory effect of dexketoprofen on the activity of cyclooxygenase-1 and cyclooxygenase-2 has been demonstrated in animals and humans.

Clinical efficacy and safety.

Clinical studies have shown that dexketoprofen exerts effective analgesic action, which develops within 30 minutes after administration of the medicinal product and lasts for 4–6 hours.

Pharmacokinetics.

Absorption.

After oral administration of dexketoprofen trometamol, maximum plasma concentration (Cmax) is achieved within 30 minutes (15–60 minutes).

When dexketoprofen trometamol is administered with food, the area under the plasma concentration-time curve (AUC) remains unchanged; however, Cmax is reduced and the absorption rate is decreased (time to reach maximum concentration [tmax] is prolonged).

Distribution.

The distribution time and elimination half-life of dexketoprofen trometamol are 0.35 and 1.65 hours, respectively. Due to the high degree of binding to plasma proteins (99%), the mean volume of distribution of dexketoprofen trometamol is less than 0.25 L/kg. Pharmacokinetic studies with multiple dosing showed that after the last dose of dexketoprofen trometamol, AUC was no higher than after a single dose, demonstrating the absence of accumulation (lack of drug accumulation).

Biotransformation and elimination.

After administration of dexketoprofen trometamol, only the S(+)-enantiomer is detected in urine, confirming the absence of its inversion into the R(–)-enantiomer in the human body.

Elimination of dexketoprofen occurs mainly via glucuronidation followed by renal excretion.

Clinical characteristics.

Indications.

Symptomatic treatment of mild to moderate pain, such as musculoskeletal pain, painful menstruation (dysmenorrhea), and dental pain.

Contraindications.

• Hypersensitivity to the active substance or to any other NSAID, or to any of the excipients of the medicinal product.

• Use in patients in whom substances with a similar mechanism of action, e.g., acetylsalicylic acid and other NSAIDs, have caused asthma attacks, bronchospasm, acute rhinitis, or led to the development of nasal polyps, urticaria, or angioedema.

• History of photoallergic or phototoxic reactions during treatment with ketoprofen or fibrates.

• Gastrointestinal bleeding or perforation in history associated with the use of NSAIDs.

• Active peptic ulcer/gastrointestinal bleeding, or any history of gastrointestinal bleeding, ulcer, or perforation.

• Chronic dyspepsia.

• Active bleeding or increased bleeding tendency.

• Crohn’s disease or ulcerative colitis (nonspecific).

• Severe heart failure.

• Moderate or severe renal impairment (creatinine clearance ≤ 59 mL/min).

• Severe hepatic impairment (Child–Pugh score 10–15 points).

• Hemorrhagic diathesis or other coagulation disorders.

• Severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake).

• Third trimester of pregnancy and lactation period (see section "Use during pregnancy or breastfeeding").

Interaction with other medicinal products and other forms of interaction.

The drug interactions listed below generally apply to the class of NSAIDs.

Unwanted combinations:

• Other NSAIDs, including selective cyclooxygenase-2 inhibitors and high-dose salicylates (≥ 3 g/day): concomitant use of multiple NSAIDs increases the risk of gastrointestinal ulcers and bleeding due to synergistic effects.
• Anticoagulants: NSAIDs enhance the effect of anticoagulants, e.g., warfarin, due to the high degree of plasma protein binding of dexketoprofen, as well as due to inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use cannot be avoided, it should be carried out under medical supervision with careful monitoring of relevant laboratory parameters.
• Heparin: increased risk of bleeding (due to inhibition of platelet function and damage to the gastric and duodenal mucosa). If concomitant use cannot be avoided, it should be conducted under medical supervision with careful monitoring of relevant laboratory parameters.
• Corticosteroids: increased risk of peptic ulcers and gastrointestinal bleeding.
• Lithium preparations (reports with several NSAIDs): NSAIDs increase lithium blood levels up to toxic values by reducing its renal excretion. Therefore, lithium levels in blood should be monitored at the start of dexketoprofen therapy, during dose adjustment, or upon discontinuation of the drug.
• Methotrexate when administered at high doses (15 mg/week or more): increased methotrexate blood levels due to reduced renal excretion, leading to hematotoxic effects.
• Hydantoin derivatives and sulfonamides: possible increase in toxicity of these substances.

Combinations requiring precautions:

• Diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists. Dexketoprofen reduces the effectiveness of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), further deterioration of renal function may occur when drugs that inhibit cyclooxygenase activity (NSAIDs), ACE inhibitors, angiotensin II receptor antagonists, and aminoglycoside antibiotics are used concomitantly. This deterioration is usually reversible.

When combining dexketoprofen with diuretics, adequate hydration must be ensured, and renal function should be monitored at the beginning and periodically during treatment. Concomitant use of dexketoprofen and potassium-sparing diuretics may lead to hyperkalemia. Monitoring of serum potassium concentration is required.

• Methotrexate when administered at low doses (< 15 mg/week): possible increase in hematotoxic effects due to reduced renal excretion; if such combination is necessary, weekly blood count monitoring is required during the first weeks of treatment, especially in patients with even mild renal impairment and in elderly patients.
• Pentoxifylline: increased risk of bleeding; therefore, patient observation and more frequent monitoring of bleeding time are required.
• Zidovudine: risk of increased toxic effects of zidovudine on erythropoiesis (toxic effect on reticulocytes), potentially leading to severe anemia within one week after starting NSAID therapy; therefore, blood analysis with reticulocyte count monitoring is required during the first 1–2 weeks after initiation of NSAID therapy.
• Sulfonylurea derivatives: NSAIDs may enhance the hypoglycemic effect of sulfonylurea drugs by displacing them from plasma protein binding sites.

Medicinal products for which caution is advised when used in combination with Dexketoprofen-Vista:

• Beta-blockers: their antihypertensive effect may be reduced due to inhibition of prostaglandin synthesis.

• Cyclosporine and tacrolimus: enhanced nephrotoxic effects of these drugs due to the effect of NSAIDs on prostaglandin synthesis; regular monitoring of renal function is required when using such combinations.

• Thrombolytic agents: increased risk of bleeding.

• Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

• Probenecid: increased plasma concentration of dexketoprofen due to reduced renal tubular secretion and glucuronidation; dose adjustment of dexketoprofen may be required in such cases.

• Cardiac glycosides: their plasma concentration may increase.

• Mifepristone: there is a theoretical risk that prostaglandin synthesis inhibitors may alter the effectiveness of mifepristone. Some data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not negatively affect the action of mifepristone or prostaglandins—specifically cervical ripening or uterine contractility—and does not reduce the clinical efficacy of medical abortion.

• Quinolone antibiotics: animal studies have shown that high-dose quinolone antibiotics in combination with NSAIDs increase the risk of seizures.

• Tenofovir: concomitant use with NSAIDs may increase blood urea nitrogen and creatinine levels; therefore, renal function should be monitored to control potential synergistic effects on kidney function.

• Deferasirox: concomitant use with NSAIDs may increase gastrointestinal toxicity and requires careful clinical monitoring.

• Pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, caution is advised when administering higher NSAID doses. Patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min) should avoid concomitant use with NSAIDs for 2 days before and 2 days after pemetrexed administration.

Special precautions for use

Dexketoprofen-Vista should be used with caution in patients with a history of allergic reactions.

Concomitant use of this medicinal product with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided. Adverse effects of the drug can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Gastrointestinal safety

When using NSAID-class medicinal products, peptic ulcers with or without perforation, and gastrointestinal bleeding (including fatal cases) may develop in the gastrointestinal tract. These adverse events may occur at any time during treatment, with or without preceding symptoms, and are independent of the presence of severe gastrointestinal disorders in the patient's history. If gastrointestinal bleeding or peptic ulceration develops during treatment with dexketoprofen, therapy with the drug should be discontinued immediately.

The risk of developing the aforementioned adverse reactions increases proportionally with higher NSAID doses and in patients with a history of gastric or duodenal ulcer, as well as in elderly patients.

During treatment with the drug, physicians should closely monitor patients due to the potential for gastrointestinal bleeding. Before initiating treatment with dexketoprofen trometamol and in patients with a history of esophagitis, gastritis, and/or peptic ulcer disease, it is necessary—as with other NSAIDs—to ensure that these conditions are in remission. Patients with existing gastrointestinal symptoms or gastrointestinal disorders in their history require monitoring for the development of gastrointestinal complications, particularly gastrointestinal bleeding.

NSAIDs should be prescribed with caution to patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as there is a risk of exacerbation.

To reduce the risk of gastrointestinal adverse reactions, physicians may prescribe gastroprotective agents (misoprostol, proton pump inhibitors). This also applies to patients requiring concomitant low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications.

Patients should be informed that they must report any discomfort in the abdominal area (particularly gastrointestinal bleeding), especially at the beginning of treatment, to their physician.

Caution is required if the patient is receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

Renal safety

The drug should be administered with caution to patients with impaired renal function, as NSAID use may lead to deterioration of kidney function, fluid retention, and edema. Due to the increased risk of nephrotoxicity, the drug should be used cautiously in patients receiving diuretics or in those who may develop hypovolemia. During treatment, patients should receive adequate fluid intake to prevent dehydration, which may exacerbate renal toxicity.

Like all NSAIDs, the drug may increase plasma concentrations of blood urea nitrogen and creatinine. These changes may be related to adverse renal effects, potentially leading to glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure. Renal function impairment occurs more frequently in elderly patients.

Hepatic safety

The drug should be administered with caution to patients with impaired liver function. Like other NSAIDs, the drug may cause transient, mild elevations in certain liver parameters, as well as marked increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. If significant increases in these parameters occur, therapy should be discontinued.

Hepatic function impairment occurs more frequently in elderly patients.

Cardiovascular and cerebrovascular safety

Patients with arterial hypertension and/or mild to moderate heart failure require monitoring and medical supervision. Particular caution is required when treating patients with a history of heart disease, especially previous episodes of heart failure, as treatment with the drug increases the risk of heart failure: fluid retention and edema have been observed during NSAID therapy. Clinical studies and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and over prolonged periods) may slightly increase the risk of arterial thrombosis (e.g., myocardial infarction or stroke). Data to exclude this risk with dexketoprofen are insufficient. Therefore, in cases of uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, dexketoprofen should be prescribed only after careful assessment of the patient's condition. Similarly careful evaluation is required before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

All non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. Therefore, dexketoprofen trometamol is not recommended for patients taking medications affecting hemostasis, such as warfarin, other coumarin derivatives, or heparins. Cardiovascular system dysfunction occurs more frequently in elderly patients.

Skin reactions

Rare cases of serious skin reactions (some with fatal outcomes) have been reported during NSAID use, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The highest risk occurs at the beginning of treatment: most cases develop within the first month of therapy.

If early signs of skin rash, mucosal lesions, or other symptoms of hypersensitivity appear, Dexketoprofen-Vista should be discontinued.

Masking symptoms of underlying infections

Dexketoprofen may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby complicating disease progression. Such symptom masking has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When dexketoprofen is used to relieve pain associated with infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Elderly patients

Elderly individuals have an increased risk of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and gastrointestinal tract perforation, which may be fatal. These patients should initiate treatment with the lowest effective dose (see section "Dosage and administration").

Elderly patients more frequently suffer from impaired renal, cardiovascular, or hepatic function (see section "Dos游戏副本 and administration").

Other information

Special caution is required when prescribing the drug to patients:

• with hereditary porphyrin metabolism disorders (e.g., acute intermittent porphyria);
• with dehydration;
• immediately after major surgical procedures.

If prolonged use of dexketoprofen is deemed necessary by the physician, regular monitoring of liver and kidney function and blood parameters is recommended.

Rare cases of severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If early signs of severe hypersensitivity reactions occur after taking Dexketoprofen-Vista, treatment should be discontinued. Depending on symptoms, appropriate treatment in such cases should be administered under medical supervision.

Patients suffering from bronchial asthma in combination with chronic rhinitis, chronic sinusitis, and/or nasal polyps have a higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to other patients. Administration of this drug may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

In exceptional cases, severe infectious complications of the skin and soft tissues may occur during varicella. Currently, there are insufficient data to fully exclude the role of NSAIDs in exacerbating this infectious process. Therefore, the use of Dexketoprofen-Vista should be avoided in varicella.

This medicinal product should be used with caution in patients with blood coagulation disorders, systemic lupus erythematosus, and mixed connective tissue diseases.

Children

The safety of using the drug in children and adolescents has not been established.

This medicinal product contains less than 1 mmol of sodium (27.1 mg) per tablet, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

The medicinal product Dexketoprofen-Vista is contraindicated during the third trimester of pregnancy and during lactation (see section "Contraindications").

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. According to epidemiological studies, the use of drugs that inhibit prostaglandin synthesis during early pregnancy increases the risk of miscarriage, congenital heart defects, and abdominal wall defects in the fetus. The absolute risk of cardiovascular malformations increases from <1% to approximately 1.5%. It is believed that the risk of such events increases with higher drug doses and longer treatment duration. In animal studies, prostaglandin synthesis inhibitors increased pre- and post-implantation losses and embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of fetal developmental abnormalities, including cardiovascular malformations, was observed. However, animal studies with dexketoprofen did not reveal toxic effects on reproductive organs.

From the 20th week of pregnancy, the use of Dexketoprofen-Vista may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there are reports of arterial duct constriction after treatment in the second trimester, most of which resolved after stopping treatment. Therefore, Dexketoprofen-Vista should not be prescribed during the first and second trimesters of pregnancy, except in cases of extreme necessity. If Dexketoprofen-Vista is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible. Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to Dexketoprofen-Vista for several days starting from the 20th week of pregnancy. Dexketoprofen-Vista use should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester, all prostaglandin synthesis inhibitors may cause:

Risks for the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• impaired renal function (see above);

Risks for the mother at the end of pregnancy and for the newborn:

• possible prolongation of bleeding time due to inhibition of platelet aggregation, even with low-dose drug use;
• inhibition of uterine contractility, leading to prolonged labor and delayed delivery.

Lactation period

There are no data on the passage of dexketoprofen into breast milk. The medicinal product Dexketoprofen-Vista is contraindicated during breastfeeding.

Fertility

Like all other NSAIDs, dexketoprofen trometamol may reduce female fertility and therefore is not recommended for women planning pregnancy. For women experiencing infertility or undergoing fertility investigations, discontinuation of the drug should be considered.

If dexketoprofen is taken by a woman trying to conceive or during the first and second trimesters of pregnancy, the lowest effective dose should be used for the shortest possible duration.

Ability to affect reaction speed when driving or operating machinery

During treatment with Dexketoprofen-Vista, adverse reactions such as dizziness, visual disturbances, or drowsiness may occur, which can reduce reaction speed and impair the ability to drive or operate machinery.

Method of Administration and Dosage

Dosage

Adults

Depending on the type and intensity of pain, the recommended dose is 12.5 mg (½ film-coated tablet) every 4–6 hours or 25 mg (1 film-coated tablet) every 8 hours. The daily dose should not exceed 75 mg.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to relieve symptoms (see section "Special Instructions"). The medicinal product Dexketoprofen-Vista is not intended for long-term therapy; treatment should be limited to the period during which symptoms persist.

Elderly patients. It is recommended to initiate therapy with low doses. The daily dose is 50 mg. If the medicinal product is well tolerated, the dose may be increased to the usual level. Due to the potential risk of adverse reactions (see section "Special Instructions"), elderly patients should be under particularly careful medical supervision.

Hepatic impairment. In patients with mild to moderate hepatic dysfunction, treatment should be initiated with the lowest recommended dose and under strict medical supervision. The daily dose is 50 mg. The medicinal product Dexketoprofen-Vista is contraindicated in patients with severe hepatic impairment.

Renal impairment. In patients with mild renal impairment (creatinine clearance 60–89 mL/min), the initial total daily dose should be reduced to 50 mg.

Dexketoprofen-Vista is contraindicated in patients with moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min).

Method of Administration

Tablets should be taken with sufficient fluid (e.g., a glass of water). Concomitant intake with food slows drug absorption (see section "Pharmacokinetics"); therefore, in acute pain, the medicinal product should be taken at least 15 minutes before meals.

Children.

The use of dexketoprofen trometamol in children has not been studied; therefore, safety and efficacy in children and adolescents have not been established. The medicinal product should not be administered to children and adolescents.

Overdose.

Symptoms of overdose are unknown. Similar medicinal products may cause gastrointestinal disturbances (vomiting, anorexia, abdominal pain) and nervous system effects (drowsiness, vertigo, disorientation, headache).

In case of accidental overdose, symptomatic treatment should be initiated immediately according to the patient's clinical condition. If an adult or child has ingested a dose exceeding 5 mg/kg body weight, activated charcoal should be administered within 1 hour. Hemodialysis may be used to eliminate dexketoprofen.

Adverse reactions

The table below lists adverse reactions whose association with dexketoprofen trometamol, based on clinical data, is considered at least possible, as well as adverse reactions reported during the post-marketing period.

Adverse reactions are categorized by organ systems and frequency of occurrence. Frequencies are defined as follows: very common (> 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and not known (cannot be estimated from available data).

The most commonly observed adverse reactions are gastrointestinal in nature. In particular, peptic ulcer, gastrointestinal perforation or bleeding may occur, sometimes with fatal outcome, especially in elderly patients. According to available data, during treatment with dexketoprofen, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease may occur. Gastritis is observed less frequently.

Also, during treatment with NSAIDs, edema, arterial hypertension, and heart failure may develop.

As with other NSAIDs, aseptic meningitis may occur, primarily in patients with systemic lupus erythematosus or mixed connective tissue disease, as well as blood-related reactions (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia).

Bullous reactions are possible, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

According to results of clinical trials and epidemiological data, the use of certain NSAIDs, especially at high doses and with prolonged treatment, moderately increases the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after marketing authorization of a medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy to the State Expert Center of the Ministry of Health of Ukraine via the following link: https://aisf.dec.gov.ua/

Shelf life. 2 years.

Storage conditions. Store at a temperature not exceeding 25 °C in the original packaging to protect from light. Keep out of reach of children.

Packaging. 10 tablets per blister; 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer.

SAG MANUFACTURING, S.L.U.

Manufacturer's address and location of its business activity.

Carretera Nacional 1 Km 36, San Agustín del Guadalix, 28750 Madrid, Spain.